Islamic Azad University
Faculty of Agriculture
A Thesis Submitted in Partial Fulfillment of the Requirments For
the Degree of M.sc(Ph.D)in Food scienc and technology
Investigation on Rheological Behaviour of Dually Modified Cassava Starch/k-Carrageenan as Gelatin Alternative in Pharmaceutical Hard Capsules
Abdorreza Mohammadi Nafchi, PhD
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Table 4.2: Gelation temperatures, TGEL and melting temperature TM (G’= G”) during cooling from 50 to 25 °C and heating from 25 to 50 °C. The rate of heating or cooling was 1°C/min. Frequency: 1 rad/s. Strain amplitude: 1%. 86
Table 4. 4: Gelling temperatures (TGEL) and melting temperatures (TM) of κ-carrageenan alone and the mixture HHSS12-κ-carrageenan determined from cooling and heating ramps at 1 °C/min and 1 rad/s. 104
Table 4.5: Storage and loss moduli G’ and G” of κ-carrageenan alone and HHSS12-κC0.5 mixture determined from temperature ramps during cooling and heating at 1 °C/min by rheological measurements. Frequency: 1 rad/s. 111
Figure 2. 4: Water content at equilibrium of pharmaceutical hard empty gelatin capsules in relationship with the mechanical behavior. The capsules are stored at different relative humidities for two weeks at 20 ° C. 16
Figure 2. 6: Test for fragility of the capsules: the percentage of broken capsules according to their water content. a: resistance to pressure with capsules filled with corn starch. b: impact resistance with empty capsules. 19
Figure 2. 19: Change in transition temperature Tm at cooling κ-carrageenan based on the total concentration of CT different monovalent cations (1) Rb+, (2) Cs+, (3) K+ ,(4) NH4+, (7) N(CH3)4+ (8) Na+, (9) Li+ and divalent cations (5-6) Ba2+, Ca2+, Sr2+, Mg2+, Zn2+, Co2+. 57
Figure 2. 20: Phase diagram of κ-carrageenan representing the variation of transition temperature on cooling and heating according to the total concentration of potassium (Rochas, 1982; Rochas & Rinaudo, 1980). 59
Figure 2. 22: Variations of G’ and G” as a function of temperature for a concentration of 1% κ-carrageenan, Frequency 1 Hz, Tg: temperature of gelation, Tm: melting temperature. Cooling G’ (■), G” (¨). Heating G’ (□), G” (◊). (Fernandes, Gonçalves & Doublier, 1992). 63
Figure 4.4: Storage and loss moduli G¢, G² as a function of temperature during a heating ramp of a 25% gelatin sample. Temperature was ramped from 25 °C to 50 °C at 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1%.. 85
Figure 4.8: Flow curves of hydrolyzed hydroxypropylated cassava starch dispersions at a concentration of 25% (g/g): HHSS6 (●), HHSS12 (■), HHSS18 (o), HHSS24 (). Measurements were performed at 50 °C.. 91
Figure 4.11: Mechanical spectra of different dually modified cassava starches at concentrations of 25%: a) HHSS6, b) HHSS12, c) HHSS18, d) HHSS24. G’: filled symbols, G”: empty symbols. Measurement temperature was 50 °C and strain amplitude was 1%.. 94
Figure 4.17: Mechanical spectrum of κC0.5 (solid lines ■, □), HHSS12 (solid lines ●, ○), and the mixture κC0.5-HHSS12 (■, □). Concentration of HHSS12 alone was 25% and in combination total concentration was 25%. G’: filled symbols, G”: empty symbols. Measurement temperature: 50 ° C. Strain amplitude: 1%.. 101
Figure 4.18: Variation of viscoelastic modulus G’ and G” as a function of temperature for κC0.5 and for the mixture of κC0.5 and HHSS12. a) Cooling from 50 °C to 20 °C. b) Heating from 20 °C to 50 °C. Heating/cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1%.. 103
Figure 4.19: Variations of modulus G’ and G” as a function of temperature during cooling from 50 °C to 20 °C for 25% HHSS24 alone and in combination with κ-carrageenan. G”: filled symbols; G’: empty symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1%.. 105
Figure 4.20: Variations of modulus G’ and G” as a function of temperature during cooling from 50 °C to 20 °C for 1% κ-carrageenan and 25% starch mixtures. G’: empty symbols; G”: filled symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1%.. 106
Figure 4.21: Variations of modulus G’ and G” as a function of temperature during heating from 20 °C to 60 °C for 1% κ-carrageenan and 25% starch mixtures. G’: empty symbols; G”: filled symbols. Cooling rate: 1 °C/min. Frequency: 1 rad/s. Strain amplitude: 1%.. 107
Figure 4. 23: Mechanical spectrum of κC0.5 (●, ○), 25% HHSS12 (dashed line with ▲, Δ) and the mixture of κC0.5-HHSS12 (■, □) at 20°C. G’: filled symbols, G”: empty symbols. Strain amplitude: 0.1% for mixtures and 1% for constituents. 109
Figure 4.24: Mechanical spectrum of mixtures HHSS12-κC1(▲, Δ), HHSS12-κC0.5 (dashed line with ●, ○) and HHSS12-κC0.25 (■, □) at 20 °C. G’: filled symbols, G”: empty symbols. Strain amplitude: 0.1% 110
With the goal of finding an alternative to gelatin in the processing of pharmaceutical capsules, the effects of k-carrageenans on dually modified cassava starch were investigated. While film forming and mechanical properties are important in all pharmaceutical capsules, solubility at high solid concentration and thermo-reversibility are important factors for hard capsule processing. Casava starches were modified first by hydrochloric acid (0.14 N for 6, 12, 18, and 24 h at 50 °C) and secondly by propylene oxide (10, 20, and 30% of solid for 24 h at 40°C).
To improve the gel setting property of the dually modified starch, dually modified cassava starches were combined with k-carrageenan (0.25, 0.5, 0.75, and, 1%). The concentration of the K+ ion in the composite mixture was adjusted appropriately to achieve the same sol-gel transition temperature. The rheological properties of the mixtures were measured and compared, with gelatin as the reference material. The solution viscosity, sol-gel transition, and mechanical properties of the films made from the mixtures at 50 °C were comparable to those of gelatin. The viscoelastic moduli (G’ and G”) for the gel mixtures were lower than those of gelatin. The composite gels had temperatures of gelation similar to that of gelatin. Both viscosity in solution and stiffness in gels could be adjusted using high levels of κ-carrageenan and was relatively independent of the molecular weight of the starch. These results illustrate that dually modified cassava starch in combination with k-carrageenan has properties similar to those of gelatin, thus these starches can be used in dip-molding processes, such as those used to make pharmaceutical hard capsules.
The capsule is one of the formulations of the oldest pharmaceutical in history, known especially from the ancient Egyptians. In Europe, it was not until the nineteenth century that the first gelatin pharmaceutical capsule with the patent of Mr. Dublanc pharmacist and his student Mr. Mothes. Over the years, this invention has been so successful that the production of capsules has grown rapidly in many countries. This has led to many improvements including the invention of hard gelatin capsules in 1846 by Mr. Lehuby (Podczeck & Jones, 2004).
The development of pharmaceutical capsules, used for therapeutic purposes, originates in the keen interest shown by the numerous researches in pharmacology. This has greatly expanded the range of possible formulations using pharmaceutical capsules. Today, pharmaceutical capsules are mainly based on animal gelatin from porcine or bovine. Gelatin is an animal protein that is a traditional ingredient in many fields, including food. Gelation properties at temperatures close to room temperature and formation of homogeneous films, potable, gelatin as a choice for the manufacturing of pharmaceutical capsules.
However, the use of animal gelatin in the food and pharmaceutical industry is governed by regulations becoming more stringent. The precautionary principal applied, for example, the risk of transmission by animal gelatin; the bovine spongiform encephalopathy (BSE) has questioned its use. Even if today the rules on the origin of the gelatin are very strict and that gelatin is no longer a risk to health, development of alternative products of interest to pharmaceutical and food industries. The sources from which gelatin can also be problematic for ethical or religious populations. Many people around the world do not consume products made from pork (vegetarians, Hebrews, and Muslims) or beef base (vegetarian Hindus). It is therefore that the replacement of gelatin with other texturing agents of non-animal origin has been much research in recent years.
The most important properties that potable gelatin as capsule forming material are heat sealability of films for soft capsule processing and solubility in high concentration, film formability and thermo-reversibility for making hard capsules.
Starch as a plant based material is one of possible alternative for gelatin due to cost and accessibility. Native starches can form films, but the films have not heat sealability, also starches are non soluble biopolymer, and form non-reversible gels. So changes or supporting the structure likely improve the starch property to consider as gelatin replacement in some cases.
The proposed system is a mixture of starch and k-carrageenan. Starch would give the mixture of film-forming properties and solubility in aqueous and carrageenan bring its ability to gel. The selected starch has focused on the use of such modification(s) on starch that able it to dissolve at temperatures below 100 °C and form stable solutions at high concentrations (≈ 20-30%). The botanical origin of the cassava starch is due to its proper amylose content, which improves mechanical properties of films and availability of this starch in Southeast Asia. The gelling agent has been studied was κ-carrageenan/K+ for its ability to form thermo reversible gels and easily adjustable thermo-physical transition temperatures. The film-forming mixtures were prepared by casting method.
The main objective of this research project is to replace the gelatin with a composite cassava (tapioca) starch film for manufacturing of pharmaceutical capsules especially hard capsules. The idea for hard capsule processing is to develop a new system whose characteristics in the solution and solid state would be closer to existing formulations. The constraints imposed industrial development concentrated formulations (25-30%) prepared at temperatures below 100 °C capable of forming a gel by physical cooling and forming a film after drying.
تعداد صفحه : 146
قیمت :14700 تومان